Description:

Objective:

The objective of this research project is to investigate the mechanisms by which phytochemicals (benzyl isothiocyanate [BIT], dimethyl fumarate [DMF], allyl disulfide [ADS], genistein [GEN], and lycopene [LYC], that naturally occur in fruits and vegetables, function in a chemoprotective role in early stages of carcinogenesis.

Approach:

The HT29 human carcinoma cell line is a model to investigate the mechanisms by which dietary phytochemicals function in a chemoprotective role during the early initiation stages of carcinogenesis. The normally proliferative HT29 cells also can be studied in the differentiated state by treatment with sodium butyrate (NaB). It has been demonstrated that treatment with NaB induces the expression of glutathione S-transferase (GST)and NAD(P)H:quinone oxidoreductase (NQO1). DMF and BIT increase GST and NQO1 and decrease cell proliferation. ADS, GEN, and LYC exhibit antiproliferative effects on HT29 cells. These studies will determine concentrations and treatment regimens for BIT, DMF, ADS, GEN, and LYC that cause differentiation and increased expression of GST and NQO1 in HT29 cells. Other studies have determined that p21, a cell cycle regulatory protein, is an absolute requirement for the NaB-mediated growth arrest observed in HT29 cells. Additional studies will determine whether treatment with BIT, DMF, ADS, GEN and LYC will cause an increased expression of p21 in HT29 cells. These studies also will explore the possibility of a relationship between the expression of p21 and the altered expression of GST and NQO1 in HT29 cells.

Expected Results:

This study is expected to determine the molecular mechanisms by which the phytochemicals impart their chemoprotective influence and to consider the implications for dietary intervention to decrease the risk of developing colon cancer and for the human population in general.

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.